TNKS1BP1 was originally identified as an interaction protein of tankyrase 1, which belongs to the poly(ADP-ribose) polymerase (PARP) superfamily. PARP members play important roles for example in DNA repair, telomere stability and mitosis regulation. Although the TNKS1BP1 protein was considered to be a poly(ADP-ribosyl)ation acceptor of tankyrase 1, its function is still unknown. Here we firstly...

Common cryptographic methods, especially Public Key Crypto Systems, PKCS based on difficulty to factor large integers or to compute the discrete logarithm, commonly deployed today will not resist attacks using quantum computers once these are operational. However, there are alternatives like hash based digital signature schemes, lattice based cryptography, or multivariate-quadratic-equations pu...

In this paper we describe attacks on PKCS#11 devices that we successfully mounted by interacting with the low-level APDU protocol, used to communicate with the device. They exploit proprietary implementation weaknesses which allow attackers to bypass the security enforced at the PKCS#11 level. Some of the attacks leak, as cleartext, sensitive cryptographic keys in devices that were previously c...

Cryptographic APIs like PKCS#11 are interfaces to trusted hardware where keys are stored; the secret keys should never leave the trusted hardware in plaintext. In PKCS#11 it is possible to give keys conflicting roles, leading to a number of key-recovery attacks. To prevent these attacks, one can authenticate the attributes of keys when wrapping, but this is not standard in PKCS#11. Alternativel...

The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) regulates the nonhomologous end joining pathway for repair of double-stranded DNA (dsDNA) breaks. Here, we present a 7A resolution structure of DNA-PKcs determined by cryo-electron microscopy single-particle reconstruction. This structure is composed of density rods throughout the molecule that are indicative of alpha helices and rev...

The current study tested the anti-hepatocellular carcinoma (HCC) cell activity of TIC10, a first-in-class small-molecule tumor necrosis (TNF)-related apoptosis-inducing ligand (TRAIL) inducer. TIC10 exerted potent anti-proliferative and pro-apoptotic actions in primary and established human HCC cells. TIC10 blocked Akt-Erk activation, leading to Foxo3a nuclear translocation, as well as TRAIL an...

Three phosphatidylinositol-3-kinase-related protein kinases implement cellular responses to DNA damage. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and ataxia-telangiectasia mutated respond primarily to DNA double-strand breaks (DSBs). Ataxia-telangiectasia and RAD3-related (ATR) signals the accumulation of replication protein A (RPA)-covered single-stranded DNA (ssDNA), which is ...

Constitutive activation of the Rearranged during Transfection (RET) proto-oncogene leads to the development of MEN2A medullary thyroid cancer (MTC). The relatively clear genotype/phenotype relationship seen with RET mutations and the development of MEN2A is unusual in the fact that a single gene activity can drive the progression towards metastatic disease. Despite knowing the oncogene responsi...

22 A subset of cellular DNA hairpins at double strand breaks is processed by 23 DNA-PKcs and Artemis-associated endonuclease. DNA hairpin termini of 24 adeno-associated virus (AAV) are processed by DNA repair machinery; however, how and 25 what cellular factors are involved in the process remains elusive. Here we show that 26 DNA-PKcs and Artemis open AAV inverted terminal repeat (ITR) hairpin ...